{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:32:42Z","timestamp":1791829962949,"version":"4.3.4"},"reference-count":72,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","award":["P1-0189"],"award-info":[{"award-number":["P1-0189"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objectives: A novel two-step flow-through in vitro lipolysis model was developed for the evaluation of drug release from a self-microemulsifying drug delivery system (SMEDDS). Methods: Firstly, the SMEDDS was dispersed in an acidic medium. Subsequently, the pH was increased, and a lipolytic reaction was immediately initiated, accompanied by medium flow onset. The latter enabled increase of the initial low pH of the medium, improving the physiological relevance of the method by simulating dosage form retainment in the stomach and transfer to the duodenum, which is very important for a weakly basic active pharmaceutical ingredient (API) incorporated in an SMEDDS. Results: Conversely to the traditional pH-stat in vitro lipolysis, the developed method is not established on titration, as the reaction vessel pH is regulated by a medium flow and buffer capacity. Individual parameters, such as pancreatin activity, buffer capacity, and medium shift, were researched using traditional pH-stat in vitro lipolysis prior to their implementation in the flow-through setup. Conclusions: The concentration of the solubilized model API, carvedilol, was increased as pancreatin activity decreased and as buffer capacity increased. The ratios between release profiles obtained under different conditions utilizing the pH-stat and novel two-step flow-through in vitro lipolysis were comparable; however, the differences were more pronounced in the flow-through method.<\/jats:p>","DOI":"10.3390\/pharmaceutics17050545","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:38:37Z","timestamp":1745390317000},"page":"545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Advancement of In Vitro Lipolysis: Two-Step Flow-Through Method for the Evaluation of Lipid-Based Drug Delivery Systems"],"prefix":"10.3390","volume":"17","author":[{"given":"Katarina","family":"Rede","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjana","family":"Ga\u0161perlin","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3653-2696","authenticated-orcid":false,"given":"Marija","family":"Bogataj","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Bolko Seljak","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.addr.2019.06.010","article-title":"In Vitro Digestion Models to Evaluate Lipid Based Drug Delivery Systems; Present Status and Current Trends","volume":"142","author":"Berthelsen","year":"2019","journal-title":"Adv. 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